What causes vitiligo and how is it treated?

Vitiligo: Causes and Treatment

Vitiligo is primarily an autoimmune disease characterized by the destruction of melanocytes, resulting in depigmented patches of skin due to a combination of genetic predisposition, environmental triggers, and immune dysregulation. 1, 2

Pathophysiology of Vitiligo

Autoimmune Mechanisms

• Vitiligo shows strong evidence of autoimmunity with:
  • Presence of circulating melanocyte-specific antibodies
  • Association with other autoimmune diseases (especially thyroid disorders)
  • Familial trait in approximately 18% of cases 1
  • Genetic predisposition involving multiple genes 3

Key Pathogenic Factors

1. Oxidative Stress

   • Melanin synthesis naturally produces reactive oxygen species (ROS)
   • Melanocytes in vitiligo patients show increased susceptibility to oxidative damage
   • Defects in antioxidant pathways (particularly the Nrf2 pathway) contribute to ROS accumulation 4

2. Cellular Stress Responses

   • Unfolded protein response (UPR) activation in stressed melanocytes
   • Release of inflammatory chemokines (IL-6, IL-8) that recruit immune cells 3

3. Immune Attack

   • CD8+ T cells target and destroy melanocytes
   • IFN-γ/CXCL10 axis drives disease progression
   • Tissue-resident memory T cells maintain the disease and cause relapses 5

4. Environmental Triggers

   • Sunburn
   • Mechanical trauma (Koebner phenomenon)
   • Chemical exposures (particularly phenolic compounds)
   • Psychological stress 2, 3

Clinical Presentation and Diagnosis

Types of Vitiligo

• Non-segmental vitiligo (NSV): Most common form, characterized by symmetrical patches that evolve over time
• Segmental vitiligo (SV): Unilateral or band-shaped lesions that progress rapidly but stabilize early 6

Diagnosis

• Diagnosis is straightforward in classical symmetrical types and can be made in primary care
• Atypical presentations require dermatologist referral 1
• Wood's light examination helps delineate areas of pigment loss, especially in lighter skin types 1
• Thyroid function testing should be considered due to high prevalence of autoimmune thyroid disease in vitiligo patients 1

Treatment Approaches

Topical Treatments

• Potent or very potent topical steroids:
  • First-line for recent-onset vitiligo
  • Limited to 2-month trial periods due to risk of skin atrophy 1, 2
• Topical calcineurin inhibitors (tacrolimus, pimecrolimus):
  • Alternative to topical steroids with better safety profile
  • Particularly useful for facial and genital areas 1, 2

Phototherapy

• Narrowband UVB (NB-UVB):
  • Recommended for widespread vitiligo or cases with significant quality of life impact
  • Preferred over PUVA due to greater efficacy and safety
  • Particularly effective for darker skin types
  • Should be monitored with serial photographs every 2-3 months 1, 2

Surgical Interventions

• Reserved for stable vitiligo (no new lesions, no Koebner phenomenon, and no extension for at least 12 months)
• Split-skin grafting provides better cosmetic results than minigraft procedures
• Autologous epidermal suspension applied to laser-abraded lesions followed by NB-UVB or PUVA therapy 2

Advanced Options

• Depigmentation therapy with p-(benzyloxy)phenol (monobenzyl ether of hydroquinone):
  • Only for severely affected patients (>50% depigmentation)
  • For those who cannot achieve repigmentation 1, 2

Psychological Support

• Vitiligo can cause significant psychological distress, social isolation, and depression
• Psychological assessment and support should be integrated into treatment plans
• Cognitive behavioral therapy can improve coping mechanisms 2

Treatment Challenges

• Natural history shows step-wise progression with periods of activity and inactivity
• Spontaneous repigmentation is uncommon
• Maintaining repigmentation is difficult (lost in up to 40% of cases) 7
• Treatment response varies significantly between individuals
• No treatment has been proven to alter the natural history of vitiligo 1

Special Considerations

• In lighter skin types (I and II), cosmetic camouflage and sunscreens may be sufficient
• Systemic therapy with oral dexamethasone is not recommended due to unacceptable side effects 1
• Treatment expectations should be realistic, as complete repigmentation is often difficult to achieve

By understanding the complex autoimmune and oxidative stress mechanisms behind vitiligo, clinicians can better approach treatment with a focus on both halting disease progression and promoting repigmentation while addressing the significant psychological impact of this visible condition.